A region of myocardium will be rendered hypoxic without restricting coronary blood flow by perfusing the left anterior descending coronary artery (LAD) of the working, in situ canine heart with deoxygenated blood. Autologous blood will be deoxygenated by an isolated lung which will be ventilated with hypoxic or anoxic gas mixtures. Coronary perfusion with hypoxic blood will limit extracellular accumulation of metabolites such as H ion, K ion, adenosine, and lactate, which are released from hypoxic myocardium and may themselves directly alter coronary hemodynamics and myocardial function. Thus, the effects of myocardial hypoxia per se can be evaluated. Coronary vascular resistance (LAD perfusion pressure divided by LAD blood flow) will be examined as arterial PO2 is decreased at normal and elevated blood flow rates. Concurrently, regional measurements will be made of myocardial PO2 (polarographic technique), contractility (Walton-Brody strain gauge), and coronary venous PO2. Observations made during hypoxic perfusion will be compared with the effects of ischemia due to reduced or stopped coronary blood flow. During hypoxic perfusion, the transmural distribution of blood flow will be determined (microsphere technique) at various perfusion flow rates, and these flow distributions will be compared with transmural flow distributions of well-oxygenated blood under conditions of flow restriction or metabolic dilation (reactive hyperemia). Collateral coronary blood flow (microsphere technique) into the perfused region will be measured during coronary occlusion and during perfusion of the region with hypoxic blood in order to determine if hypoxia per se opens collateral channels in the absence of interarterial pressure gradients. Regional coronary venous blood will be sampled to determine if hypoxia increases passage of microspheres through arteriovenous shunts in the coronary circulation.